1. Field of This Invention
This invention involves the production of 4-hydroxy-6-hydroxymethyl-pyrimidines, and more particularly the production of such compounds from the corresponding chloromethyl pyrimidines.
2. Prior Art
6-HYDROXYMETHYL PYRIMIDINES HAVE BEEN PRODUCED FROM THE CORRESPONDING 6-CHLOROMETHYLPYRIMIDINES. In such cases the 6-chloromethyl compound is first converted to the 6-acetoxymethyl derivative by treatment with an aqueous silver acetate solution, and this derivative is then converted by heating with barium hydroxide in water to the 6-hydroxymethyl derivative (Zentralblatt, 1913, II, page 273). Such a process is cumbersome and requires a reaction of two stages. Furthermore, large quantities of silver acetate are consumed.
Synthetic Methods of Organic Chemistry, (W. Teilheimer, Publishers of S. Krager, Basel) 2 76 No. 237, teaches that 5-chloromethyl furfural is poured into a large quantity of boiling water so that the concentration of the developing HCl will be so weak that it will not react with the reaction product. 5-oxymethyl furfural results with a yield of 90 percent. (W. N. Haworth and W. G. M. Jones, Soc. 1944, p 667, is cited as the source.) The reaction is: ##EQU3##
Journal of the American Chemical Society, 73, pp. 2,388 to 91 (1951), teaches the following reaction: ##EQU4## The purity was only 90 percent after two crystallization steps during its purification.
Dutch Pat. No. 126,387 teaches a process of preparing 4-chloropyrimidines (and their salts) having the following formula: ##EQU5## wherein: R.sub.1 signifies an alkyl radical with at most 4 carbon atoms; R.sub.2 an alkylene radical with at most 4 carbon atoms; R.sub.3 signifies a chlorine atom; X signifies a direct bond or an alkylene radical with at most 4 carbon atoms; R.sub.4 signifies a phenyl radical substituted by one or more halogen atoms, alkyl, alkoxy, or alkenyloxy groups, with each having at most 4 carbon atoms, amino, alkylamino groups with at most 4, or dialkylamino groups with altogether at most 8 carbon atoms; and R.sub.5 signifies a halogen atom, an alkyl or alkoxy group with at most 4 carbon atoms, a hydroxyl group, amino group, alkylamino group with at most 4, or a dialkylamino group with altogether at most 8 carbon atoms, or an alkylene amino group interrupted possibly by oxygen with at most 7 ring atoms. The products are pharmacologically active. That Dutch patent is based on Dutch Patent Application No. 6,503,747 (Ciba) and was published prior to examination.
A typical process is: ##EQU6## See for example, column 17, example XIV.
That Dutch patent also teaches a process for the production of pharmaceutical preparations by the mixing of a pharmacologically effective substance of a compound (obtained by the process of the Dutch patent) with a carrier.
Attention is also drawn to: U.S. Pat. No. 3,048,587; Brown, "The Pyrimidines", Interscience Publishers, (1962), pp. 214-5; Brown, "The Pyrimidines -- Supplement I", Interscience Publishers, (1970), p. 161; McCasland, G. E. et al., J. Am. Chem. Soc. 68 (1946); and British Patent No. 471,416.